We have shown that infusion of norepinephrine (NE, 2 microgram/min/kg for 90 min) in the rabbit produces a cardiomyopathy with extensive myofiber necrosis. This is largely prevented if the animals are pretreated with insulin (5 units/kg). We propose to examine the mechanical performance of this model using isolated muscle and intact heart preparations. Effects of steroids will be compared with insulin and responsiveness to graded doses of catecholamines will be studied in the NE injured preparations. These studies will be extended to acute and chronic diabetic models. The effects of the diabetic state on the performance of these preparations will be determined. Sensitivity to catechol injury will be judged by comparison with non-diabetic hearts. Changes in NE dose-response relations will also be sought. The possibility that the insulin deficient diabetic rabbit is susceptible to endogenous catecholamine injury will be tested by comparing myocardial performance in diabetics subjected to beta blockade with practolol. All hearts will be examined histologically and the extent of myofiber injury compared with performance measurements. Work now in progress to develop a stable chronic diabetic lamb model will be extended to provide more complete characterization of these animals as they grow and mature.